Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
152
Countries
1
Sites
12
Severe asthma exacerbations in partial and uncontrolled preschool asthma
The primary objective is to evaluate whether addition of Tiotropium via Respimat® to ICS prevents severe asthma exacerbations.
Key facts
- Sponsor
- Goethe University Frankfurt
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Respiratory Tract Diseases [C08]
- Trial duration
- 18 Feb 2022 → 2 Apr 2025
- Decision date (initial)
- 2024-06-05
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Federal Ministry for Education and Research (BMBF), Germany · Boehringer Ingelheim, Germany
External identifiers
- EU CT number
- 2024-513916-84-00
- EudraCT number
- 2021-000190-81
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
The primary objective is to evaluate whether addition of Tiotropium via
Respimat® to ICS prevents severe asthma exacerbations.
Secondary objectives 1
- The secondary objective is to evaluate whether addition of Tiotropium via Respimat® to ICS reduces health utilization (hospitalizations, physician visits, antibiotic use) in partial or uncontrolled preschool asthma.
Conditions and MedDRA coding
Severe asthma exacerbations in partial and uncontrolled preschool asthma
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Male or female patients with preschool asthma aged between 1 and 5 years (< 6 at visit 1). In addition, age-appropriate assent in accordance with local regulations or guidelines or both before enrolment in the study and prior to the beginning of any study-specific procedures will be obtained from the child.
- Physician diagnosed asthma of at least 6 months' history of asthma symptoms, including (but not limited to) wheezing, cough, and/or shortness of breath.
- All patients must have been on maintenance treatment with an ICS at a stable dose, either as mono treatment or in combination with another controller medication, for at least 4 weeks before visit 1.
- Patient was hospitalized due to acute severe asthma and/or was treated with at least 2 courses of systemic steroids (three days of oral steroids or one day of rectal prednisolone 100mg (Rectodelt®)) in the last 24 months before visit 1.
- All patients must be symptomatic (partly controlled or uncontrolled) as defined by the GINA guideline for children aged 5 years and younger in the four weeks prior to screening (visit 1) and randomization (visit 2) despite treatment with ICS (visit 1 and visit 2).
- Patients must be able to inhale from the Respimat® inhaler (with a spacer).
Exclusion criteria 4
- Patients with a significant disease other than asthma such as, but not limited to, the following diagnoses: cystic fibrosis, bronchopulmonary dysplasia, primary immunodeficiency, congenital heart disease, parasitic disease, and foreign body aspiration.
- Patients with clinically relevant abnormal screening hematology or blood chemistry will be excluded if the abnormality defines a significant disease as defined in exclusion criterion.
- Patients with known hypersensitivity to anticholinergic drugs, or any other components of the Tiotropium inhalation solution.
- Patients with any severe acute asthma exacerbation or severe respiratory tract infection defined by systemic steroid intake or hospitalization in the four weeks prior to visit 1.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Time to first severe exacerbations, defined by hospitalization and/or at least 3 days of systemic steroids or one day of rectal prednisolone (Rectodelt®).
Secondary endpoints 13
- number of severe exacerbations
- number of hospitalizations (severe exacerbation)
- (severe) exacerbation-free survival time
- number of asthma-related events defined by use of antibiotics
- percentage of night-time awakenings due to asthma symptoms as assessed by the electronic patients diary/PACD
- percentage of days without asthma symptoms assessed by TIPP diary App (PACD)
- percentage of days and episodes of > 3 days with use of PRN salbutamol rescue medication
- health utilization (number of physician visits)
- number of missed days in daycare
- result of TRACK
- CGI-C at end of treatment and potential biomarkers for treatment response
- Eosinophils, IgE, specific IgE to common allergens (birch, grass, Dermatophagoides pteronyssinus, Alternaria, Cladosporium, cat, dog, hen's egg, cow's milk and peanut
- Assessment of safety: Safety will be ensured by analysis of symptom scores and rescue medication use by the electronic diary, and adverse events (AEs).
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Tiotropium bromide monohydrate
PRD11140893 · Product
- Active substance
- Tiotropium Bromide Monohydrate
- Substance synonyms
- TIOTROPIUM BROMIDE HYDRATE
- Pharmaceutical form
- SOLUTION FOR INHALATION
- Route of administration
- INHALATION USE
- Max daily dose
- 2.5 µg microgram(s)
- Max total dose
- 912.5 µg microgram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- BOEHRINGER INGELHEIM INTERNATIONAL
- Paediatric formulation
- No
- Orphan designation
- No
Placebo 1
Respimat® Inhaler one cartridge of Placebo
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Goethe University Frankfurt
- Sponsor organisation
- Goethe University Frankfurt
- Address
- Theodor-Stern-Kai 7
- City
- Frankfurt Am Main
- Postcode
- 60590
- Country
- Germany
Scientific contact point
- Organisation
- Goethe University Frankfurt
- Contact name
- TIPP LKP Zentrum
Public contact point
- Organisation
- Goethe University Frankfurt
- Contact name
- TIPP LKP Zentrum
Locations
1 EU/EEA country · 12 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ended | 152 | 12 |
| Rest of world | — | 0 | — |
Investigational sites
Praxis für Kinderpneumologie und Allergologie
Praxis für Kinderpneumologie und Allergologie, Praxis für Kinderpneumologie und Allergologie, Collinistraße 11, Mannheim
Universitaetsmedizin Goettingen
Klinik für Pädiatrische Kardiologie, Intensivmedizin und Neonatologie, Robert-Koch-Strasse 40, Weende, Goettingen
Evangelisches Klinikum Bethel gGmbH
Universitätsklinik für Kinder- und Jugendmedizin, Klinisches Studienzentrum Pneumologie, Allergologie, Bielefeld
Universitaetsklinikum Jena KöR
Pädiatrische Pneumologie, Am Klinikum 1, Lobeda, Jena
Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
Klinik und Poliklinik für Kinder- und Jugendmedizin, Fetscherstrasse 74, Johannstadt-Nord, Dresden
Universitaet Leipzig
Universitätsklinik für Kinder- und Jugendmedizin, Liebigstrasse 20a, Zentrum-Suedost, Leipzig
Evangelisches Krankenhaus Duesseldorf
Klinik für Kinder und Jugendliche, Kirchfeldstrasse 40, Unterbilk, Duesseldorf
Universitaetsklinikum Augsburg
Klinik für Kinder- und Jugendliche, Stenglinstrasse 2, Kriegshaber, Augsburg
Charite Universitaetsmedizin Berlin KöR
Klinik für Pädiatrie m.S. Pneumologie und Immunologie mit Intensivmedizin, Augustenburger Platz 1, Wedding, Berlin
Universitaetsklinikum Frankfurt AöR
Klinik für Kinder- und Jugendmedizin, Theodor-Stern-Kai 7, 60590, Frankfurt Am Main
Klinikum der Universitaet Muenchen AöR
Dr. von Haunerschen Kinderspital, Lindwurmstrasse 4, Ludwigsvorstadt-Isarvorstadt, Munich
Medizinische Hochschule Hannover
Pädiatrische Pneumologie, Allergologie und Neonatologie, Carl-Neuberg-Strasse 1, Gross Buchholz, Hanover
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Germany | 2022-02-18 | 2022-02-21 | 2024-02-29 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-28440
- Halt date
- 2024-02-29
- Member states concerned
- Germany
- Publication date
- 2024-06-06
- Reason
- Sponsor decision
- Explanation
- The recruitment period in TIPP—and therefore the study—has already been extended by 12 months.
Since the patients will be treated for 12 months and since the funding period ends in April 2025, it must be ensured that the last patient will complete the study in March 2025.
Beyond April 2025, no more financial resources will be available. Last-patient-in will be on February 29th, 2024; last patient-out will be on March 31st, 2025.
At the end of recruitment, all patients are treated in accordance with the protocol. Therefore, the premature termination of patient recruitment has no impact on these patients, as they can complete the study as planned in the protocol.
Regarding the final statistical analysis, we achieve a lower power but the evaluation will still take place. - Follow-up measures
- Patient will be treated according to protocol.
- Benefit-risk balance changed
- No
- Treatment stopped
- No
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| TIPP - ICH-E3 Report Synopsis_2025-10-02_redacted SUM-100442
|
2025-10-02T15:32:08 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| TIPP - Lay summary_DE-2025-10-02 | 2025-10-02T15:26:14 | Submitted | Laypersons Summary of Results |
Documents 4 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | TIPP - Lay summary_DE-2025-10-02 | 1 |
| Summary of results (for publication) | APPENDIX 1 - TIPP Trial schedule_2025-10-02 | 1 |
| Summary of results (for publication) | APPENDIX 2 - TIPP CONSORT Flowchart_2025-10-02 | 1 |
| Summary of results (for publication) | TIPP - ICH-E3 Report Synopsis_2025-10-02_redacted | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-05-22 | Germany | Acceptable 2024-05-31
|
2024-06-05 |